Journal of Translational Medicine | |
Novel HER2 Aptamer Selectively Delivers Cytotoxic Drug to HER2-positive Breast Cancer Cells in Vitro | |
Xian-Da Yang3  Xin Lu1  Feng-Dan Wang1  Jie Ma2  Yong-Mei Song2  Jin-Hong Duan3  Zhe Liu3  | |
[1] Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100073, China;Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China;Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China | |
关键词: Tumor targeted therapy; Breast cancer; HER2; Aptamer; | |
Others : 1205933 DOI : 10.1186/1479-5876-10-148 |
|
received in 2012-02-27, accepted in 2012-07-20, 发布年份 2012 | |
【 摘 要 】
Background
Aptamer-based tumor targeted drug delivery system is a promising approach that may increase the efficacy of chemotherapy and reduce the related toxicity. HER2 protein is an attractive target for tumor-specific drug delivery because of its overexpression in multiple malignancies, including breast, gastric, ovarian, and lung cancers.
Methods
In this paper, we developed a new HER2 aptamer (HB5) by using systematic evolution of ligands by exponential enrichment technology (SELEX) and exploited its role as a targeting ligand for delivering doxorubicin (Dox) to breast cancer cells in vitro.
Results
The selected aptamer
was an 86-nucleotide DNA molecule that bound to an epitope peptide of HER2 with a Kd of 18.9 nM. The aptamer also bound to the extracellular domain (ECD) of HER2 protein with a K
d
of 316 nM
, and had minimal cross reactivity to albumin or trypsin. In addition, the aptamer was found to preferentially bind to HER2-positive but not HER2-negative breast cancer cells. An aptamer-doxorubicin complex (Apt-Dox) was formulated by intercalating Dox into the DNA structure of HB5. The Apt-Dox complex could selectively deliver Dox to HER2-positive breast cancer cells while reducing the drug intake by HER2-negative cells in vitro. Moreover, Apt-Dox retained the cytotoxicity of Dox against HER2-positive breast cancer
cells, but reduced the cytotoxicity to HER2-negative cells.
Conclusions
The results suggest that the selected HER2 aptamer may have application potentials in targeted therapy against HER2-positive breast cancer cells
.
【 授权许可】
2012 Liu et al.; licensee BioMed Central Ltd.
【 预 览 】
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